The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems

Abstract Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated...

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Autores principales:	Nagasuryaprasad Kotikalapudi, Samuel Joshua Pragasam Sampath, Sinha Sukesh Narayan, Bhonde Ramesh R, Harishankar Nemani, Sathish Kumar Mungamuri, Vijayalakshmi Venkatesan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ddcc500f44e4b2686b49fe7751e74e2
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spelling	oai:doaj.org-article:0ddcc500f44e4b2686b49fe7751e74e22021-12-02T16:45:54ZThe promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems10.1038/s41598-021-96121-02045-2322https://doaj.org/article/0ddcc500f44e4b2686b49fe7751e74e22021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96121-0https://doaj.org/toc/2045-2322Abstract Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in pre-clinical/Ob-T2D management.Nagasuryaprasad KotikalapudiSamuel Joshua Pragasam SampathSinha Sukesh NarayanBhonde Ramesh RHarishankar NemaniSathish Kumar MungamuriVijayalakshmi VenkatesanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nagasuryaprasad Kotikalapudi Samuel Joshua Pragasam Sampath Sinha Sukesh Narayan Bhonde Ramesh R Harishankar Nemani Sathish Kumar Mungamuri Vijayalakshmi Venkatesan The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
description	Abstract Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in pre-clinical/Ob-T2D management.
format	article
author	Nagasuryaprasad Kotikalapudi Samuel Joshua Pragasam Sampath Sinha Sukesh Narayan Bhonde Ramesh R Harishankar Nemani Sathish Kumar Mungamuri Vijayalakshmi Venkatesan
author_facet	Nagasuryaprasad Kotikalapudi Samuel Joshua Pragasam Sampath Sinha Sukesh Narayan Bhonde Ramesh R Harishankar Nemani Sathish Kumar Mungamuri Vijayalakshmi Venkatesan
author_sort	Nagasuryaprasad Kotikalapudi
title	The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
title_short	The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
title_full	The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
title_fullStr	The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
title_full_unstemmed	The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
title_sort	promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0ddcc500f44e4b2686b49fe7751e74e2
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The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems

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